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Jardiance® (empagliflozin) tablets has a demonstrated safety and tolerability profile across multiple trials
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Proven safety profile in the EMPA-KIDNEY trial
Select AEs of interest (≥1% incidence) in the EMPA-KIDNEY trial1
| JARDIANCE 10 mg (n=3304) | Placebo (n=3305) | |
| Bone fracture | 4.0% | 3.7% |
| Serious acute kidney injury | 3.2% | 4.1% |
| Serious Hyperkalemia | 2.8% | 3.3% |
| Symptomatic dehydration | 2.5% | 2.3% |
| Severe dehydration | 2.3% | 2.3% |
| Serious urinary tract infection | 1.6% | 1.6% |
The safety profile in patients with CKD was generally consistent with that observed across the studied indications. In EMPA-KIDNEY, the occurrence of lower-limb amputations was reported with event rates of 2.9 events per 1000 patient-years in the placebo treatment arm and 4.3 events per 1000 patient-years in the JARDIANCE 10 mg treatment arm.
The use of JARDIANCE in combination with insulin or insulin secretagogues can increase the risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.
The safety profile in EMPA-KIDNEY was generally consistent with the overall safety profile for JARDIANCE.
EMPA-KIDNEY trial design:
A randomized, parallel-group, double-blind, placebo-controlled study of 6609 adult patients with CKD (eGFR ≥20 to <45 mL/min/1.73 m2; or eGFR=45 to <90 mL/min/1.73 m2 with uACR ≥200 mg/g), evaluating the efficacy and safety of JARDIANCE 10 mg (n=3304) vs placebo (n=3305) as adjunct to standard of care therapy. The primary endpoint was a composite of: sustained decrease in eGFR of ≥40% from baseline, sustained decrease in eGFR to <10 mL/min/1.73 m2, ESKD (the initiation of maintenance dialysis or receipt of a kidney transplant), or CV or renal death.
Across multiple trials, patients taking JARDIANCE experienced:
- Discontinuation from trial due to UTIs was 0.1% with placebo, 0.2% with JARDIANCE 10 mg, and 0.1% with JARDIANCE 25 mg
- Discontinuation from trial due to GMI occurred in 0% of placebo-treated patients and 0.2% of patients treated with either JARDIANCE 10 mg or 25 mg
Common AEs in monotherapy and combination therapy trials*
| JARDIANCE 10 mg (n=999) | JARDIANCE 25 mg (n=997) | Placebo (n=995) | |
| UTIs | 9.3% | 7.6% | 7.6% |
| UTIs: males | 3.6% | 4.1% | 3.2% |
| UTIs: females | 18.4% | 17.0% | 16.6% |
| Female GMIs | 5.4% | 6.4% | 1.5% |
| Upper respiratory tract infection | 3.1% | 4.0% | 3.8% |
| Increased urination | 3.4% | 3.2% | 1.0% |
| Dyslipidemia | 3.9% | 2.9% | 3.4% |
| Arthralgia | 2.4% | 2.3% | 2.2% |
| Male GMIs | 3.1% | 1.6% | 0.4% |
| Nausea | 2.3% | 1.1% | 1.4% |
Common AEs: Included hypoglycaemia, genital infections, UTIs, and increased urination.
The use of JARDIANCE in combination with insulin or insulin secretagogues can increase the risk of hypoglycaemia. A lower dose of insulin or insulin secretagogue may be required.
Important AEs: Post-marketing cases of DKA and necrotizing fasciitis of the perineum (Fournier’s gangrene), including life-threatening and fatal, with use of SGLT2 inhibitors, including JARDIANCE.
JARDIANCE is not recommended to improve glycaemic control in patients with T1D or in patients with T2D with eGFR <30 mL/min/ 1.73 m2; not recommended for treatment of CKD in patients with polycystic kidney disease or patients requiring/with recent history of IV immunosuppressive therapy or >45 mg of prednisone or equivalent for kidney disease.
* Adverse events, excluding hypoglycaemia, reported in pooled, placebo-controlled clinical studies in ≥2% of patients treated with JARDIANCE and greater than placebo.
Monotherapy trial design:
A Phase III, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of JARDIANCE (10 mg, 25 mg) administered orally over 24 weeks in drug-naïve patients with type 2 diabetes mellitus and insufficient glycemic control despite diet and exercise. Six hundred seventy-six treated patients received placebo (n=228), JARDIANCE 10 mg (n=224), or JARDIANCE 25 mg (n=224). The primary endpoint was A1C change from baseline. Weight change and blood pressure change from baseline were secondary endpoints.2
Add-on to metformin trial design:
A Phase III, randomized, double-blind, placebo-controlled, parallel-group, efficacy and safety study of JARDIANCE (10 mg, 25 mg) administered orally once daily over 24 weeks in patients with type 2 diabetes mellitus with insufficient glycemic control despite treatment with metformin ≥1500 mg alone. Six hundred thirty-seven treated patients received placebo + metformin (n=207), JARDIANCE 10 mg + metformin (n=217), or JARDIANCE 25 mg + metformin (n=213). The primary endpoint was A1C change from baseline. Weight change and blood pressure change from baseline were secondary endpoints.3
AE=adverse event; CKD=chronic kidney disease; CV=cardiovascular; DKA=diabetic ketoacidosis; eGFR=estimated glomerular filtration rate; GMI=genital mycotic infection; SGLT2=sodium-glucose cotransporter-2; SU=sulfonylurea; T1D=type 1 diabetes; T2D=type 2 diabetes; uACR=urinary albumin-to-creatinine ratio; UTI=urinary tract infection.
For more information, please see Prescribing Information.
References
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Herrington WG, Staplin N, Wanner C, et al; EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127.
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Roden M, Weng J, Eilbracht J, et al; EMPA-REG MONO Trial Investigators. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1(3):208-219.
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Häring HU, Merker L, Seewaldt-Becker E, et al; EMPA-REG MET Trial Investigators. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014;37(6):1650-1659.